RESUMO
BACKGROUND: Prenatal diagnosis of persistent left superior vena cava is increasing, but little is known about outcomes of infants with prenatally diagnosed isolated persistent left superior vena cava. OBJECTIVE: To assess the outcomes of infants with isolated persistent left superior vena cava diagnosed prenatally compared with infants with associated malformations. METHODS: All cases of persistent left superior vena cava confirmed by specialized fetal echocardiography in pregnant women were included from a single-centre prospective registry. Unfavourable outcome was defined as termination of pregnancy, in utero death, postnatal death or severe genetic syndrome missed prenatally. RESULTS: A total of 256 infants were included: 113 cases (44.1%) with isolated persistent left superior vena cava and 143 cases (55.9%) with associated malformations; respectively, 111 (98.2%) and 101 (70.6%) had a live birth. The median postnatal clinical follow-up was 3.6 years. Five-year postnatal survival with good outcome was estimated at: 100% (95% confidence interval 90.7% to 100%) in infants with isolated persistent left superior vena cava; 91.0% (74.0% to 98.1%) in infants with associated cardiac anomalies; 87.5% (51.8% to 97.3%) in infants with associated extracardiac anomalies; 81.0% (52.6 to 94.6%) in infants with both cardiac and extracardiac anomalies; and 78.9% (36.7% to 95.9%) in infants with non-structural anomalies. All genetic findings and syndromes were detected in fetuses or infants with non-isolated persistent left superior vena cava. CONCLUSION: Infants with isolated persistent left superior vena cava have good short-term outcomes postnatally, but persistent left superior vena cava is frequently associated with other malformations that have an effect on outcomes, which should be thoroughly searched for prenatally.
Assuntos
Cardiopatias Congênitas , Veia Cava Superior Esquerda Persistente , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/genética , Humanos , Lactente , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Veia Cava Superior/anormalidades , Veia Cava Superior/diagnóstico por imagemRESUMO
INTRODUCTION: Total abnormal pulmonary venous return is a heart defect often missed prenatally, yet at birth, it is a surgical emergency. Antenatal detection could be improved by sonographic visualization of the anastomosis of 2 pulmonary veins in a sinus into the left atrium. The objective of this study is to evaluate the feasibility of this screening method. METHOD: Prospective observational study. Five operators selected one representative image taken during morphological ultrasound screening. Anonymized images were later assessed for quality by an expert. Both the operator and the expert were asked to rate the picture and collect clinical data. Feasibility corresponded to the percentage of images judged satisfactory by the expert; reliability corresponded to the percentage judged satisfactory by both the expert and the sonographer. RESULTS: A total of 192 patients were included. Feasibility was 73% (95% confidence interval, 67.1%-79.7%) and reliability was 81.4% (95% confidence interval, 75.9%-86.9%). There was no learning curve. CONCLUSION: This study confirms that visualization of the 2 pulmonary veins in a sinus into the left atrium at midtrimester screening is simple and reproducible. The next stage is to evaluate the sensitivity and specificity as a screening test of total abnormal pulmonary venous return and whether that would improve morbidity and mortality.
Assuntos
Cardiopatias Congênitas/diagnóstico por imagem , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Estudos de Viabilidade , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Recent drug crises have highlighted the complexity, benefits and risks of medication communication. The difficulty of this communication is due to the diversity of the sources of information and the target audience, the credibility of spokespersons, the difficulty to communicate on scientific uncertainties and the precautionary principle, which is influenced by variable perceptions and tolerances of the risk. Globally, there is a lack of training in risk management with a tendency of modern society to refuse even the slightest risk. Communication on medications is subject to regulatory or legal requirements, often uses tools and messages that are not adapted to the target audience and is often based on a poor knowledge of communication techniques. In order to improve this situation, the available information must be coordinated by reinforcing the unique medication information website and by coordinating communication between authorities by means of a single spokesperson. A particular effort must be made in the field of training in the proper use and risk of medications for both the general population and patients but also for healthcare professionals, by setting up a unified academic on-line teaching platform for continuing medical education on medications and their proper use.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Educação em Saúde , Pessoal de Saúde/educação , Disseminação de Informação , Barreiras de Comunicação , Bases de Dados Factuais , Serviços de Informação sobre Medicamentos , Educação Médica Continuada , Guias como Assunto , Necessidades e Demandas de Serviços de Saúde , Humanos , Prescrição Inadequada/prevenção & controle , Comportamento de Busca de Informação , Gestão de Riscos , Comportamento de Redução do Risco , Revelação da VerdadeRESUMO
We describe a case series of 4 fetuses with ectopic connections of the ductus venosus to the coronary sinus detected prospectively between August 2011 and February 2012 in 2 congenital cardiologic centers. An enlarged coronary sinus alerted the sonographer. Fetal echocardiography showed ectopic connection of the ductus venosus in an enlarged coronary sinus in all 4 cases. To our knowledge, this anatomic form of ectopic umbilical vein drainage has not previously been reported. The infants were doing well. This venous variant should be considered in cases of isolated coronary sinus dilatation after elimination of a left superior vena cava and a totally anomalous pulmonary vein connection.
Assuntos
Seio Coronário/anormalidades , Seio Coronário/diagnóstico por imagem , Anomalias dos Vasos Coronários/diagnóstico por imagem , Veias Umbilicais/anormalidades , Veias Umbilicais/diagnóstico por imagem , Ecocardiografia/métodos , Feminino , Humanos , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Gravidez , Ultrassonografia Pré-Natal/métodos , Malformações Vasculares/diagnóstico por imagem , Veia Cava Inferior/anormalidades , Veia Cava Inferior/diagnóstico por imagemRESUMO
STUDY/PRINCIPLES: Arrythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an autosomal-dominantly inherited disease caused by mutations in genes encoding desmosomal proteins and is characterised by fibrofatty replacement occurring predominantly in the right ventricle and can result in sudden cardiac death. Naxos and Carvajal syndrome, autosomal recessive forms of ARVC/D, are characterised by involvement of the right and/or left ventricle in association with palmoplantar keratoderma and woolly hair. The aim of the present study has been to screen for mutations in the desmosomal protein genes of two unrelated patients with Naxos-Carvajal syndrome. METHODS AND RESULTS: Desmosomal protein genes were screened for mutations by polymerase chain reaction as well as direct sequencing approach. In each patient we identified a single heterozygous de novo mutation in the desmoplakin gene DSP, p.Leu583Pro and p.Thr564Ile, leading to severe combined cardiac/dermatological and cardiac/dermatological/dental phenotypes. The DSP missense mutations are localised in the N terminal domain of desmoplakin. CONCLUSION: The identified variations in DSP involve highly conserved residues. Moreover, the variations are de novo mutations and they are localised in critical protein domains that appear to be mutation hot spots. We assume that these heterozygous variations are causal for the mixed Naxos-Carvajal syndrome phenotype in the screened patients.
Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Desmoplaquinas/genética , Doenças do Cabelo/genética , Ceratodermia Palmar e Plantar/genética , Mutação de Sentido Incorreto , Adolescente , Displasia Arritmogênica Ventricular Direita/diagnóstico , Feminino , Doenças do Cabelo/diagnóstico , Heterozigoto , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , MasculinoRESUMO
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and severe arrhythmogenic disorder. Although usually transmitted in a recessive form, few cases of dominant mutations have been reported. Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. We performed molecular analysis of the CASQ2 gene in 43 probands with CPVT and identified eight mutations in five patients. Six mutations were novel: one was a single nucleotide deletion, three affected consensus splice sites, and two had unknown consequences: the c.939 + 5G>C and the synonymous c.381C>T variations. We demonstrated that these two variations affected CASQ2 splicing using a splicing minigene assay. These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT.
Assuntos
Calsequestrina/genética , Aconselhamento Genético , Mutação/genética , Taquicardia Ventricular/genética , Taquicardia Ventricular/terapia , Sequência de Bases , Família , Feminino , Células HEK293 , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Splicing de RNARESUMO
The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.
Assuntos
Tratamento Farmacológico/estatística & dados numéricos , Farmacoeconomia/legislação & jurisprudência , Legislação de Medicamentos/tendências , Preparações Farmacêuticas/economia , França , Legislação de Medicamentos/economiaRESUMO
The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas. First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.